This project seeks to determine the potential cariogenicity of human dental plaque microorganisms other than Streptococcus mutans by using a sequential screening procedure in animal model systems. The primary screen will involve hamsters receiving high sucrose Diet 2000. Representative strains of organisms which do not colonize the hamster on Diet 2000 will be retested in hamsters receiving a different cariogenic diet with a lower sucrose level. The final screen will be performed using monoinfections in gnotobiotic rats. In this way it is expected that it will be possible to identify any plaque organism which may contribute to caries development in humans. In addition to identifying potentially cariogenic plaque organisms, studies will be performed to determine biochemical and other cell characteristics which are associated with cariogenicity. This will include study of factors which enhance or diminish virulence of these organisms and the study of the effects of inhibitors of specific microbial metabolic reactions in vitro and in vivo. Organisms which are not readily identifiable by colonial morphology on selective media will be "labelled" by induction of streptomycin resistance to facilitate determinations of how well they are able to colonize the hamster dentition since this would be a key prerequisite for any cariogenic microorganism. The use of a final screen in gnotobiotic rats will permit distinctions to be made between organisms which have no inherent cariogenic potential and those which do but are unable to establish themselves in the mixed microbial environment indigenous to the hamster.